Implants are used in modern medical technology in a variety of embodiments. They serve to support blood vessels, hollow organs and duct systems (endovascular implants), to fasten and temporarily secure tissue implants and tissue transplants, but also for orthopedic purposes, e.g., as nails, plates or screws, among other things.
Implantation of stents is one of the most effective therapeutic measures in treatment of vascular diseases. The purpose of stents is to assume a supporting function in a patient's hollow organs. Stents of a traditional design therefore have a filigree supporting structure comprising metallic struts, which are initially in a contracted form for introducing them into the body and are widened at the site of application. One of the main areas of application of such stents is for permanently or temporarily widening vascular constrictions and keeping them open, in particular stenoses of coronary vessels. In addition, aneurysm stents are also known for supporting damaged vascular walls.
The base body of each implant, in particular of a stent, comprises an implant material. An implant material is a nonviable material that interacts with biological systems and is used for administration in medicine. The basic prerequisites for using a material as an implant material, which comes in contact with the physical environment when used as intended, is its physical compatibility (biocompatibility). Biocompatibility is understood to be the ability of a material to induce a suitable tissue reaction in a specific application. This includes adaptation of the chemical, physical, biological and morphological surface properties of an implant to the recipient tissue with the goal of achieving a clinically desired interaction. The biocompatibility of an implant material also depends on the reaction of the biosystem in which it is implanted over time. For example, irritation and inflammation occur in a relatively short period of time and may lead to tissue changes. Biological systems thus react in different ways, depending on the properties of the implant material. According to the reaction of the biosystem, implant materials can be subdivided into bioactive, bioinert and degradable/absorbable materials. For the purposes of the present invention, only degradable/absorbable metallic implant materials, which are referred to below as biocorrodible metallic materials, are of interest.
The use of biocorrodible metallic materials is recommended in particular because an implant must often remain only temporarily in the body to fulfill the medical purpose. Implants of permanent materials, i.e., materials that do not degrade in the body, may have to be removed again because rejection reactions in the body may occur in the medium range and long range, even when there is a high biocompatibility.
One approach to prevent an additional surgical procedure thus consists of making the implant entirely or in part of a biocorrodible metallic material. Biocorrosion is understood to refer to processes which are caused by the presence of endogenous media and lead to a gradual degradation of the structure of which the material is comprised. At a certain point in time, the implant or at least the part of the implant made of the biocorrodible material, loses its mechanical integrity. The degradation products are mostly absorbed by the body. As in the case of magnesium, for example, in the best case the degradation products even have a positive therapeutic effect on the surrounding tissue. Small quantities of unabsorbed alloy ingredients can be tolerated.
Known biocorrodible metallic materials include pure iron and biocorrodible alloys of the main elements magnesium, iron, zinc, molybdenum and tungsten. DE 197 31 021 A1 proposes that medical implants should be made of a metallic material whose main ingredient is an element from the group of alkali metals, alkaline earth metals, iron, zinc and aluminum. Alloys based on magnesium, iron and zinc are described as being especially suitable. Secondary constituents of the alloys may be manganese, cobalt, nickel, chromium, copper, cadmium, lead, tin, thorium, zirconium, silver, gold, palladium, platinum, silicon, calcium, lithium, aluminum, zinc and iron.
EP 1 419 793 B1 describes the use of a biocorrodible magnesium alloy containing >90 wt % magnesium, 3.7-5.5 wt % yttrium, 1.5-4.4 wt % rare earth metals and the remainder <1 wt % to produce a stent.
EP 1 842 507 A1 describes an implant of a base body consisting of an yttrium-free and gadolinium-containing magnesium alloy. The alloy may also contain neodymium (Nd), zinc (Zn), zirconium (Zr) and calcium (Ca). The alloy preferably contains 1.0 to 5.0 wt % Gd and 1.0 to 5.0 wt % Nd to keep the cytotoxicity at a low level and to improve the mechanical properties such as strength, hardness and ductility as well as the processability of the material. The Zn and Zr content preferably amount to 0.1 to 3.0 wt % each to ensure a homogeneous distribution of the elements in the alloy.
Biodegradable vascular supports (stents) made of magnesium alloys have already been tested in clinical studies. A magnesium alloy containing yttrium and rare earths, technical designation WE43, has been used. When using this alloy, which has already been tested in other areas of implantology in animal experiments, some properties still pose problems in a physiological environment. Specifically, these WE alloys have a tendency to degrade rapidly in physiological media, trigger an excessive release of degradation products into the surrounding tissue and an excessive release of hydrogen at the site of implantation. In addition, these alloys manifest unwanted reactions in the process of manufacturing the implants. It has been found that repeated thermomechanical shaping processes in the production of precursors—for example, in manufacturing tubes for the production of stents by tube drawing or by extrusion—can significantly impair the processability and the mechanical properties of the material.